α-Hydroxy-β-amino acids (isoserines) are important targets because these amino acids are present in molecules of great biological interest such as the new lipopeptidic siderophore named ornicorrugatin,1 KRI-1314,2 a potent human renin inhibitor polypeptide, amastatin,3 a tetrapeptide with immunoregulatory, antitumor, and antibacterial activity, microginin,4 threo-β-benzyloxyaspartate (TBOA),5 the 1st non-transportable blocker for all subtypes of EAATs and, most of all, in taxan derivatives6.
From the steric point of view, the biological requests of the above amino acids are well defined and the threo (2R,3S) isomers are in general active and thus preferred.
Synthetic approaches for the preparation of compounds of isoserines through the C-2/C-3 bond formation are known by reaction of a sulfinylimine with the litium enolate of a protected α-hydroxy-ester7a,b or of a simple imine with the litium enolate of an ester followed by an oxidative process.7c The main drawback of the above reactions are in the first case7a,b the use of expensive sulfinylimines whose synthesis is not easy. In the second case only moderate yields are obtained and an oxidative step with an expensive reagent (oxaziridine) is required to introduce the α-hydroxy group. According to another synthetic approach7d, simple imine derivatives are made to react with α-methoxyketene silylacetal in acidic conditions. Isoserine compounds, functionalized with a α-OMe group are formed in moderate yield and diastereoselection. Furthermore the α-OMe group must be deprotected in a separate step. Finally, the condensation of N-arylimines with dangerous aryldiazoacetates in high stoichiometric excess and promoted by an expensive rhodium catalyst is known.7e Isoserine derivatives are obtained with variable diastereoselection depending on the substitution pattern and in moderate yields. A major difficulty which affects all the known synthetic methods is to obtain a pure enantiomer because all methods, except rif. 7d, use a chiral auxiliary in the starting reagent/s, thus generating four diastereoisomers in the condensative process.